Prion protein expression in human leukocyte differentiation.
The cellular isoform of the prion protein (PrPC) is a small glycoprotein attached to the outer leaflet of the plasma membrane by a glycosylphosphatidylinositol anchor. This molecule is involved in the pathogenesis of prion diseases in both humans and animals. We have characterized the expression patterns of PrPC during human leukocyte maturation by flow cytometry with monoclonal antibodies to PrPC, the glycan moiety CD15, and the stem cell marker CD34. We observe that prion protein is present on CD34+ bone marrow (BM) stem cells. Although lymphocytes and monocytes maintain PrPC expression throughout their differentiation, PrPC is downregulated upon differentiation along the granulocyte lineage. In vitro retinoic acid-induced differentiation of the premyeloid line HL-60 into granulocyte-like cells mimics the suppression of PrPC in granulocyte differentiation, as both PrPC mRNA and protein are downregulated. These data suggest that selected BM cells and peripheral mononuclear cells may support prion agent replication, because this process is dependent on availability of PrPC. Additionally, retinoic acid-induced extinction of PrPC expression in HL-60 cells provides a potential model to study PrP gene regulation and protein function. Finally, these data suggest the existence of cell-specific glycoforms of PrPC that may determine cellular susceptibility to infection by the prion agent.
Dodelet
V C
VC
Department of Microbiology and Immunology, Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada.
Cashman
N R
NR
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D005434:Flow Cytometry; D006098:Granulocytes / Q000737:chemistry; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000737:chemistry* / Q000166:cytology*; D016256:Lewis X Antigen / Q000032:analysis; D008214:Lymphocytes / Q000737:chemistry; D009000:Monocytes / Q000737:chemistry; D011328:Prions / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D016256:Lewis X Antigen; D011328:Prions; D012333:RNA, Messenger; D014212:Tretinoin